Sideri, Theodora C. and Koloteva-Levine, Nadejda and Tuite, Mick F. and Grant, Chris M. (2011) Methionine Oxidation of Sup35 Protein Induces Formation of the [PSI+] Prion in a Yeast Peroxiredoxin Mutant. Journal of Biological Chemistry, 286 (45). pp. 38924-38931. ISSN 0021-9258. (doi:https://doi.org/10.1074/jbc.M111.272419) (Full text available)
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The frequency with which the yeast [PSI+] prion form of Sup35 arises de novo is controlled by a number of genetic and environmental factors. We have previously shown that in cells lacking the antioxidant peroxiredoxin proteins Tsa1 and Tsa2, the frequency of de novo formation of [PSI+] is greatly elevated. We show here that Tsa1/Tsa2 also function to suppress the formation of the [PIN+] prion form of Rnq1. However, although oxidative stress increases the de novo formation of both [PIN+] and [PSI+], it does not overcome the requirement of cells being [PIN+] to form the [PSI+] prion. We use an anti-methionine sulfoxide antibody to show that methionine oxidation is elevated in Sup35 during oxidative stress conditions. Abrogating Sup35 methionine oxidation by overexpressing methionine sulfoxide reductase (MSRA) prevents [PSI+] formation, indicating that Sup35 oxidation may underlie the switch from a soluble to an aggregated form of Sup35. In contrast, we were unable to detect methionine oxidation of Rnq1, and MSRA overexpression did not affect [PIN+] formation in a tsa1 tsa2 mutant. The molecular basis of how yeast and mammalian prions form infectious amyloid-like structures de novo is poorly understood. Our data suggest a causal link between Sup35 protein oxidation and de novo [PSI+] prion formation.
|Divisions:||Faculties > Sciences > School of Biosciences|
|Depositing User:||Sue Davies|
|Date Deposited:||27 Mar 2012 14:38 UTC|
|Last Modified:||10 Jun 2014 11:00 UTC|
|Resource URI:||https://kar.kent.ac.uk/id/eprint/29209 (The current URI for this page, for reference purposes)|